title: Chronic treatment with melatonin attenuates serotonergic degeneration in the striatum and olfactory tubercle of zitter mutant rats.
abstract: The effects of chronic treatment with the antioxidant hormone melatonin on degeneration of serotonergic fibers were studied in the striatum and olfactory tubercle of the zitter rat, which shows a loss-of-function mutation of the glycosylated transmembrane protein attractin. In these animals, serotonergic fibers in the striatum and olfactory tubercle undergo spontaneous and progressive degeneration as a result of abnormal metabolism of reactive oxygen species. Homozygous zitter (zi/zi) rats were provided ad libitum access to drinking water containing melatonin for 9 months (M) after weaning. High-performance liquid chromatography analysis revealed that melatonin treatment significantly increased serotonin in the caudate-putamen, (CPU), nucleus accumbens (NA) and olfactory tubercle (OT). Immunohistochemical staining for serotonin was consistent with the neurochemical data and further demonstrated substantially increased numbers of serotonergic nerve terminals in these areas. Aberrant serotonergic fibers characterized by swollen varicosities (>1 microm in diameter) were observed in the CPU and NA of 10 M zi/zi rats. The number of these fibers decreased after melatonin treatment ended. Furthermore, hyperinnervation of serotonergic fibers was observed in the OT of melatonin-treated zi/zi rats. These results suggest that melatonin protects serotonergic fibers and terminals in zitter rats and/or promotes their neuroplasticity.
authors.affiliation: Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, Mubu, Tochigi 321-0293, Japan. shu-ueda@dokkyomed.ac.jp
authors.forename: Shiuchi
authors.initials: S
authors.lastname: Ueda
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Taro
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Naitoh
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
mesh_terms: D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000097:blood / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000235:genetics*; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009833:Olfactory Pathways / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C492191:Atrn protein, rat; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D012701:Serotonin; D008550:Melatonin